Protein–protein interactions between
membrane-localized receptors and intracellular signalling molecules control neuronal
function and theoretically provide a rich source of vastly excluded targets for
drug discovery in neuropsychopharmacology. But, unlike the well-defined binding
pocket of transporters and receptors, the flat, expansive, and adaptive
topology of the protein–protein interface presents a sizeable challenge to the
goal of identifying small molecules that result in a gain or loss of function
of the protein-protein complex. This is offset by the growing body of evidence
to suggest that a few amino acids at the interface (‘hot spot’) contribute to
the majority of the binding energy in protein–protein interactions suggesting
that modulators with a high degree of specificity could be developed.
Furthermore, recent approaches in screening technologies and accessibility to
an ever-increasing diversity of small molecules propose that protein–protein
interactions are a viable option for drug discovery.